CAPACITY OF 1,25-DIHYDROXYVITAMIN-D TO STIMULATE EXPRESSION OF CALBINDIN-D CHANGES WITH AGE IN THE RAT

Studies in rats and humans have shown that there is an age-related dec line in the stimulation of intestinal Ca transport by 1,25 dihydroxyvi tamin Dg [1,25(OH)(2)D], the active metabolite of vitamin D. The calbi ndins are a family of vitamin D-dependent calcium-binding proteins fou nd in the intestine (calbindin D-9k) and kidney (calbindin D-28k) and are thought to play a role in calcium transport and homeostasis. The p urpose of this study was to determine if the capacity of 1,25(OH)(2)D to stimulate the expression of calbindin protein and mRNA changes with age. Young (2 months), adult (12 months), and old (22 months) male F3 44 rats were made deficient in 1,25(OH)(2)D by being fed a strontium-c ontaining diet and then being given a single ip injection of 1,25(OH)( 2)D. Calbindin protein levels were measured by immunological technique s using specific antisera, and mRNA levels were measured by Northern a nd dot blots. The maximal amount of calbindin D-9k protein induced by 1,25(OH)(2)D declined with age in the duodenum but not in the ileum. I n time-course studies, there was a delay in calbindin D-9k induction i n the duodenum but not in the ileum of adult rats compared to young ra ts. In contrast to protein induction, maximal calbindin D-9k mRNA leve ls in response to 1,25(OH)(2)D were greater in the adult animal and sh owed no time lag compared to those in the young animal. In the kidney, maximal levels of renal calbindin D-28k protein and mRNA did not chan ge with age, but there was delayed induction in the adult. These studi es demonstrate that there is an age-related decrease in the induction of calbindin protein in response to 1,25(OH)(2)D in the duodenum, but not in the ileum or kidney. This decline may be due to decreased trans lation of calbindin D-9k mRNA into protein in the duodenum with age. ( C) 1998 Academic Press.